Machine and method for producing porous membranes for medical use

ABSTRACT

The machine ( 1 ) for producing porous membranes ( 2 ) for medical use comprises a plurality of reserves ( 25   a   , 25   b   , 25   c   , 26   a   , 26   b   , 26   c ) of components ( 18   a   , 18   b   , 18   c , 19 a   , 19   b   , 19   c ) which constitute fluid substances, first and second guns ( 16, 17 ) supplied from the reserves ( 25   a   , 25   b   , 25   c   , 26   a   , 26   b   , 26   c ) for spraying the fluid substances onto an element ( 37 ) on which the substances are deposited and build up, the element ( 37 ) and the guns ( 16, 17 ) being mobile relative to one another for substantially even distribution of the fluid substances designed to form the membrane ( 2 ).

BACKGROUND OF THE INVENTION

[0001] The present invention relates to a machine and method forproducing porous membranes for medical use.

[0002] In particular, the present invention relates to a machine andmethod for producing biocompatible and heamocompatible membranesdesigned to constitute vascular prostheses and artificial tissues formedical use.

[0003] The prior art describes many techniques for the production, usingpolymers, of small-diameter porous or filamentous tubular tissues.

[0004] In addition to the now consolidated production techniques usingextrusion, a spray method for producing membranes is known, by whichthey are obtained, for example, from thermodynamically unstablepolymeric solutions. Specifically, the unstable solution is generatedwith the addition of a non-solvent to a dilute polymeric solution andthe membranes are obtained with spray deposition, using a single spraymeans, or with simultaneous but separate spray deposition of theunstable polymeric and non-solvent solution by separate spray means, ona supporting element designed to define the shape of the membrane.

[0005] The method described above allows the production, for example, ofsmall-diameter vascular prostheses or flat membranes obtained by cuttingtubular membranes with a larger diameter longitudinally.

[0006] The vascular prostheses or flat membranes, hereinafter generallyreferred to as porous membranes, obtained with the above-mentionedtechniques, although having indisputable positive aspects, are not freeof disadvantages.

[0007] The main disadvantage consists of the fact that thechemico-physical properties of the porous membranes obtained with thespray method, particularly the porosity of the membrane structure, aredifficult to control.

[0008] Generally speaking, with the known methods, it is difficult toobtain membranes able to simultaneously fulfil haemocompatibility andbiocompatibility requirements and provide adequate mechanical strength.

SUMMARY OF THE INVENTION

[0009] Therefore, the aim of the present invention is to provide amachine for producing porous membranes which are free of theabove-mentioned disadvantage and, at the same time, are practical foruse and simple and economical to produce.

[0010] Accordingly the present invention provides a machine forproducing porous membranes for medical use as described in claim 1.

[0011] Another aim of the present invention is to provide a method forproducing membranes for medical use, in particular tubular membranes,which can be used as prostheses, especially vascular prostheses, andmore specifically small-diameter vascular prostheses, the method beingsimple and flexible to implement.

[0012] Accordingly the present invention also provides a method forproducing porous membranes for medical use as described in claim 16.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The technical features of the present invention, in accordancewith the above-mentioned aims, are set out in the claims herein and theadvantages more clearly illustrated in the detailed description whichfollows, with reference to the accompanying drawings, which illustrate apreferred embodiment of the invention without limiting the scope of theinventive concept, and in which:

[0014]FIG. 1 is a schematic illustration of a preferred embodiment of amachine for producing porous membranes, made in accordance with thepresent invention;

[0015]FIG. 2 is a top perspective view of a machine for producingmembranes, made in accordance with the present invention;

[0016]FIGS. 3, 4, 5 and 6 are front elevation views of a portion of themachine illustrated in FIG. 2 in as many different operatingconfigurations;

[0017]FIGS. 7, 8 and 9 are top plan views of a portion of the machineillustrated in FIGS. 1 and 2 in as many different operatingconfigurations;

[0018]FIG. 10 is an enlarged cross-section of the detail P illustratedin FIG. 3.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] With reference to FIG. 2, the numeral 1 indicates as a whole aportion of a machine for producing porous membranes 2 made in accordancewith the present invention.

[0020] The machine 1 comprises a frame 3 and a central body 4 extendinglongitudinally in a direction D.

[0021] The central body 4 has a first and a second spindle 5, 6 whichare coaxial with one another, driven in synchronized rotation about anaxis A parallel with the direction D, by respective toothed belts 7, 8.

[0022] The toothed belts 7, 8 are in turn driven by toothed pulleys, ofwhich FIG. 2 fully illustrates only one, labeled 9, keyed to oppositeends of a shaft 10. The shaft 10 is turned by drive means of the knowntype which are not illustrated or described in any further detail.

[0023] The shaft 10 has an axis of rotation B parallel with theabove-mentioned axis A of the spindles 5, 6.

[0024] Each spindle 5, 6 supports one end of a supporting element 11. InFIG. 2 the supporting element 11 consists of a cylindrical body 12 witha small diameter.

[0025] At the side of the central body 4, the machine 1 comprises afirst carriage 13 which slides longitudinally in the direction D, onguide parts 14. A threaded rod 15 engages as it turns with the carriage13, to drive the carriage in the direction D. The threaded rod 15 isturned by drive means of the known type and not illustrated.

[0026] With reference to FIGS. 1 and 2, the first carriage 13 comprisesfirst and second guns 16, 17 with nozzles 16 a, 17 a designed to sprayfluid substances, respectively consisting of first and second mixtures18, 19.

[0027] The mixtures 18 and 19 are supplied to the guns 16, 17 throughpipes 20 by pumps 21, 22.

[0028] The mixtures 18, 19 are formed at and by mixer parts 23, 24 towhich a plurality of stored reserves of components designed to form theabove-mentioned mixtures 18, 19 are fluidly connected.

[0029] In particular, for example FIG. 1 illustrates three reserves 25a, 25 b, 25 c of components 18 a, 18 b, 18 c for the first mixture 18and three reserves 26 a, 26 b, 26 c of components 19 a, 19 b, 19 c forthe second mixture 19.

[0030] The machine 1 also comprises a source 27 of pressurized gassupplied to the guns 16, 17 by pipes 28 to activate the nozzles 16 a, 17a for spray emission of the mixtures 18, 19.

[0031] The nozzles 16 a, 17 a of the two guns 16, 17 are angled in sucha way that they substantially converge on the same point of thecylindrical body 12.

[0032] With reference to FIG. 2, on the side of the cylindrical body 12opposite the first carriage 13, the machine 1 comprises a secondcarriage 29 which also slides longitudinally in the direction D onrespective guide parts 30 and is driven by a threaded rod 15.

[0033] The second carriage 29 is covered by an extractor hood 31, one ofwhose intakes 32 is positioned over the guns 16, 17.

[0034] As shown in FIG. 1, the hood 31 is connected, by a manifoldschematically illustrated with a line 33, to a suction source, alsoschematically illustrated with a block 34.

[0035] Again with reference to FIG. 1, the machine 1 also comprises acentral control unit 35 designed to act on the above-mentioned mixerparts 23, 24 as well as the guns 16, 17 and on the drive means of thespindles 5, 6 and carriages 13, 29.

[0036] The guns 16, 17, together with the nozzles 16 a, 17 a, the source27 of pressurized gas and the pumps 21, 22 as a whole define, for themachine 1, means 36 for spraying the mixtures 18, 19.

[0037] In practice, as illustrated in FIG. 2, the cylindrical body 12 ismounted on the central body 4 of the machine 1, with its ends 12 a, 12 bfixed to the respective spindles 5, 6.

[0038] Through the above-mentioned drive means, which are notillustrated, by means of the shaft 10 and belts 7, 8, the cylindricalbody 12 which forms the supporting element 11 is turned about its axisA.

[0039] Starting with a first limit position of the first carriage 13,illustrated in FIG. 2, the first nozzle 16 a is activated by a flow ofpressurized gas from the source 27 through the pipe 28. The pressurizedgas, in accordance with known methods which are not described in anyfurther detail, causes the spray emission of the first mixture 18 fromthe nozzle 16 a, creating a first jet 16 b. The first mixture issupplied to the nozzle 16 a by the first pump 21 through the pipe 20.

[0040] The first pump 21 sends the first mixture 18 to the first nozzle16 a, drawing it from the first mixer 23 to which the three reserves 25a, 25 b, 25 c of the components 18 a, 18 b, 18 c are connected.

[0041] Similarly to the above description with reference to the firstnozzle 16 a, and substantially simultaneously with this, the secondnozzle 17 a is also activated by a flow of pressurized gas from thesource 27, through the pipe 28. The pressurized gas causes the sprayemission of the second mixture 19 from the nozzle 17 a, creating asecond jet 17 b. The second mixture 19 is supplied to the nozzle 17 a bythe second pump 22 through the pipe 20.

[0042] The second pump 22 sends the second mixture 19 to the secondnozzle 17 a, picking it up from the second mixer 24, to which the threereserves 26 a, 26 b, 26 c of the components 19 a, 19 b, 19 c areconnected.

[0043] Again starting from the limit position illustrated in FIG. 2, thefirst carriage 13 begins to move, driven by the rotation of the threadedrod 15 which as it turns engages with the carriage 13, in the directionD, as indicated by the arrow F1. At the same time, the cylindrical body12 which constitutes the supporting element 11 is turned by the spindles5, 6 about the axis A.

[0044] Similarly to the above description, the second carriage 29 beginsto move, in the direction D as indicated by the arrow F1, driven by therotation of the threaded rod 15 which as it turns engages with thecarriage 29.

[0045] The extractor hood 31, integral with the second carriage 29 alsomoves in the direction D as indicated by the arrow F1, substantiallysynchronized with the first carriage 13 and remains over the nozzles 16a, 17 a. The extractor action of the hood 31 is mainly intended topromote the regular emission of the jets 16 b, 17 b of the mixtures 18,19 directed onto the supporting element 11.

[0046] The above-mentioned movements, simultaneously with the sprayingaction of the nozzles 16 a, 17 a, allows the fluid substances consistingof the mixtures 18, 19 to be deposited on the supporting element 11, thelatter therefore constituting an element 37 on which the fluidsubstances are deposited and build up.

[0047] While the supporting element 11 carries on rotating about its ownaxis A continuously, the movement of the carriages in the direction Dcontinues with an alternating motion. That is to say, when a second,opposite limit position, not illustrated and defined by the desiredlongitudinal dimensions for the membrane 2 being formed is reached, thedirection of carriage 13, 29 movement is inverted and the movementcontinues in the direction indicated by the arrow F2.

[0048] The repetition in succession of numerous cycles of alternatingcarriage 13, 29 movement allows a given amount of the mixtures 18, 19 tobe deposited, said amount designed to form the body of the membrane 2.

[0049] In other words, according to the desired thickness of themembrane 2 and considering the mixture fluid flow rate of nozzles 16 b,17 b, the number of alternating motion feed cycles for the carriages 13,29 is established.

[0050] A first set of such feed cycles is performed by the machine 1with the mixtures 18, 19 having respective first compositions given byparticular relative quantities for mixing of the components 18 a, 18 b,18 c, 19 a, 19 b, 19 c stored in the reserves 25 a, 25 b, 25 c, 26 a, 26b, 26 c.

[0051] The values required of these first compositions are set on thecentral control unit 35 which operates directly on the mixer parts 23,24 in order to make up the first compositions.

[0052] As illustrated in FIG. 10, the mixtures 18, 19 in their firstconfigurations form a first layer 38 of the porous membrane 2, thisfirst layer 38 having predetermined chemico-physical properties.

[0053] When executing the commands set on it, the central control unit35 therefore acts on the mixer parts 23, 24 to change the relativequantities of the components 18 a, 18 b, 18 c, 19 a, 19 b, 19 c storedin the reserves 25 a, 25 b, 25 c, 26 a, 26 b, 26 c and to create thesecond compositions of the mixtures 18, 19.

[0054] The machine 1 performs a second set of cycles with the mixtures18, 19 with the second compositions.

[0055] As they are deposited on the first layer 38, the mixtures 18 and19, in their second compositions, create a second layer 39 of the porousmembrane 2, this second layer 39 having predetermined chemico-physicalproperties which are different to those of the first layer 38 below it.

[0056] In particular, as illustrated in FIG. 10, these chemico-physicalproperties include the porosity of the membrane 2 which, for examplewith reference to tubular membranes for vascular prostheses,advantageously involves two different layers, the first, internal layer38 in contact with the hematic fluid and more porous, and the second,external layer 39, more compact and with greater mechanical strength.

[0057] Advantageously, the mixers 23, 24, not illustrated in detail, areof the solenoid valve type, programmable and allow sequential valveopening so that the nozzles 16 a, 17 a can be supplied withpredetermined quantities of the components 18 a, 18 b, 18 c in thereserves 25 a, 25 b, 25 c and, at the same time, the components 19 a, 19b, 19 c in the reserves 26 a, 26 b, 26 c.

[0058] As illustrated in FIG. 3, the element 37 on which the substancesare deposited and build up is the cylindrical body 12 described abovewith reference to FIG. 2, designed for producing tubular porousmembranes 2 suitable for use as vascular prostheses even with very smalldiameters. The ends of the cylindrical body 12, not illustrated, areconnected to the machine 1 spindles 5, 6 to turn about its axis A.

[0059] With reference to FIG. 4, the element 37 on which the substancesare deposited and build up consists of a cylindrical drum 12 c with adiameter larger than that of the above-mentioned cylindrical body 12.Use of the drum 12 c as an element 37 on which the substances aredeposited and build up is intended to produce flat porous membranesobtained by cutting tubular membranes 2 produced with theabove-mentioned method longitudinally.

[0060] With reference to FIG. 5, the element 37 on which the sprayedfluid substances are deposited and build up consists of a stent 40. Thestent 40 is a tubular element, made of metal or plastic for insertion,for example, in a blood vessel to hold it open and prevent constrictionor pressure from the outside. The stent 40 is supported by a finesupporting wire 41, advantageously made of polytetrafluoroethylene,which passes inside it and whose opposite ends, not illustrated in thedrawing, are connected to the machine 1 spindles 5, 6 to turn about itsaxis A. As it turns about the axis A, the wire 41 causes the stent 40 torotate.

[0061] During normal machine 1 operation, the stent 40 is hit by one orboth of the jets 16 b, 17 b from the nozzles 16, 17 and, by means of theabove-mentioned technique, a dense membrane 2 is formed on its surface,where the term dense refers to a membrane 2 whose porosity is very low,that is to say, which is substantially closed and impermeable. Sincestents are tubular elements with gaps in the surface, the fluidsubstances sprayed can advantageously be deposited evenly on both theouter surface and in the inner tubular face, passing through the gaps inthe outer surface.

[0062]FIG. 6 illustrates a preferred embodiment of the configurationillustrated in FIG. 5. In this improved configuration, the machine 1comprises a heating element 46, schematically illustrated in thedrawing. This element 46 is located below the stent 40 which is mountedon the supporting wire 41. The heating element 46 is regulated by atemperature control unit 47 and powered by known means, not illustratedor described in further detail, for heating a zone 48 close to the stent40.

[0063] Advantageously, thanks to the heat, when the particles of fluidsubstances sprayed by the nozzles 16 a, 17 a make contact with the stent40, they form a substantially smooth and even layer on its surface.Moreover, the higher temperature created in the zone 48 by the presenceof the heating element 46 allows the solvents present in the fluidssprayed to rapidly evaporate, increasing adhesion to the stent 40 by themembrane 2 as it is formed.

[0064]FIG. 7 illustrates an alternative embodiment of the machine 1disclosed. This alternative embodiment allows the above-mentionedprocedure for spray depositing the fluid substances to be performed atthe same time as a filament 42 of a suitable strengthening material(polyester, polyurethane, silicone, etc.) is wound around the supportingelement 11. In particular, the filament 42 is incorporated in the porousmembrane 2 being formed on the rotating cylindrical body 12. Thefilament 42 is wound in a spiral, with a predetermined pitch, by therespective movements of the rotating support 12 and of a rotarydispenser element 43 for the filament 42. The element 43 can slide inthe direction D, driven by drive means which are not illustrated.

[0065]FIGS. 8 and 9 illustrate yet another embodiment of the machine 1disclosed. In this embodiment, once the nozzles 16 and 17 have depositeda predetermined quantity of the fluid substances on the cylindrical body12, providing a given porous membrane 2 thickness, a tubularstrengthening mesh 44 is inserted on the cylindrical body 12. The mesh44, advantageously made of polyester, is then covered with anothermaterial, which may or may not be porous, again deposited with the spraytechnique described above. Advantageously, the tubular mesh 44 hassubstantially wide links, allowing substantial continuity between thematerial spray-deposited before insertion of the mesh 44 and thatdeposited over the mesh 44.

[0066] Therefore, the mesh 44 is incorporated between two polymericlayers.

[0067] Where special needs require it, the tubular mesh 44 can also onlybe coated on its outer wall, by inserting the mesh 44 directly on thecylindrical body 12 without previously spray-depositing any material onthe body 12, as described above.

[0068] The strengthening filament 42 and the tubular mesh 44 togetherconstitute membrane 2 stiffening elements 45.

[0069] The operations described above with reference to FIGS. 7, 8 and 9may also be performed with large deposit and build up elements 37, suchas the cylindrical drum 12 c, to obtain strengthened flat porousmembranes 2.

[0070] Advantageously, depending on the required membrane 2 composition,the control unit 35 acts upon the mixer parts 23, 24, altering therelative quantities of components 18 a, 18 b, 18 c, 19 a, 19 b, 19 c,for example, in a substantially instantaneous way, with a steppedfunction, or continuously with a gradual function.

[0071] Advantageously, but without limiting the scope of the presentinvention, in a preferred embodiment of the present invention the firstmixture 18 comprises a polymer and the second mixture 19 comprises anon-solvent for the polymer.

[0072] The invention described can be subject to modifications andvariations without thereby departing from the scope of the inventiveconcept. Moreover, all the details of the invention may be substitutedby technically equivalent elements.

What is claimed is:
 1. A machine for producing porous membranes (2) formedical use, starting with fluid substances consisting of mixtures (18,19) of two or more components (18 a, 18 b, 18 c, 19 a, 19 b, 19 c), themachine being of the type comprising: reserves (25 a, 25 b, 25 c, 26 a,26 b, 26 c) of said components (18 a, 18 b, 18 c, 19 a, 19 b, 19 c),spray means (36) for the fluid substances, connected to the reserves (25a, 25 b, 25 c, 26 a, 26 b, 26 c), a support (11) constituting an element(37) on which the fluid substances sprayed by the means (36) aredeposited and build up, the element (37) and the spray means (36) beingmobile relative to one another for substantially even distribution ofthe fluid substances designed to form the membrane (2), the machinefurther comprising, upstream of the spray means (36), mixer means (23,24) for mixing together the components (18 a, 18 b, 18 c, 19 a, 19 b, 19c) which form the fluid substances, in the desired relative mixingquantities, these relative quantities providing the membrane (2) withgiven chemico-physical properties.
 2. The machine according to claim 1,further comprising a central control unit (35) designed to act upon themixer means (23, 24) to alter the relative quantities for mixture of thecomponents (18 a, 18 b, 18 c, 19 a, 19 b, 19 c) of the fluid substances,according to the desired values set on the control unit (35).
 3. Themachine according to claim 1 or 2, wherein the spray means (36) compriseat least a first nozzle (16 a) and a second nozzle (17 a) for spraying afirst mixture (18) and a second mixture (19) at the support (11).
 4. Themachine according to claim 3, further comprising at least one pump (21,22) for supplying the fluid substances to the nozzles (16 a, 17 a). 5.The machine according to claim 3 or 4, further comprising at least onesource (27) of pressurized gas for activating the nozzles (16 a, 17 a).6. The machine according to any of the foregoing claims from 1 to 5,wherein the support (11) comprises a cylindrical element (12, 12 c) forproducing tubular porous membranes (2), the cylindrical element (12, 12c) being designed to turn about an axis of rotation (A).
 7. The machineaccording to any of the foregoing claims from 1 to 5, wherein theelement (37) on which the fluid substances sprayed are deposited andbuild up is a stent (40) designed to be covered by the substances, thestent (40) being supported by the machine using a wire (41) passinginside it and made to rotate about an axis of rotation (A).
 8. Themachine according to claim 7, further comprising a heating element (46)designed to heat a given zone (48) close to the stent (40).
 9. Themachine according to claim 6, wherein the spray means (36) comprise afirst carriage (13) supporting the nozzles (16 a, 17 a), the firstcarriage (13) and the cylindrical element (12, 12 c) being mobilerelative to one another in a direction (D) substantially parallel withthe axis of rotation (A) of the cylindrical element (12, 12 c).
 10. Themachine according to claim 9, wherein the first carriage (13) is drivenby drive means so that it slides in the direction (D) substantiallyparallel with the axis of rotation (A) of the cylindrical element (12,12 c).
 11. The machine according to any of the foregoing claims from 6to 10, further comprising a second carriage (29) supporting an extractorhood (31), the second carriage (29) sliding in the direction (D)substantially parallel with the axis of rotation (A) and the extractorhood (31) being positioned over the nozzles (16 a, 17 a).
 12. Themachine according to any of the foregoing claims from 1 to 11, whereinone of the mixtures (18, 19) comprises a polymer and the other mixture(18, 19) comprises a non-solvent for the polymer.
 13. The machineaccording to any of the foregoing claims from 1 to 12, furthercomprising means (43) for the insertion of membrane (2) stiffeningelements (45) during membrane (2) formation.
 14. The machine accordingto claim 13, wherein the stiffening elements (45) comprise a filament(42) designed for insertion in the membrane (2).
 15. The machineaccording to claim 13, wherein the stiffening elements (45) comprise atubular mesh (44) designed for insertion in the membrane (2).
 16. Amethod for producing porous membranes (2) for medical use starting withfluid substances consisting of mixtures (18, 19) of two or morecomponents (18 a, 18 b, 18 c, 19 a, 19 b, 19 c), comprising the stepsof: supplying the fluid substances to spray means (36), depositing andbuilding up the fluid substances sprayed by the spray means (36) on asupporting means (11), providing drive means for the spray means (36)and the supporting means (11) for substantially even distribution of thesubstances designed to form the membrane (2), wherein the supply stepcomprises the further step of changing the relative quantities formixture of the components (18 a, 18 b, 18 c, 19 a, 19 b, 19 c),according to the desired values, relative to the chemico-physicalproperties required of the membrane (2).
 17. The method according toclaim 16, wherein the step of changing the relative quantities formixture of the components (18 a, 18 b, 18 c, 19 a, 19 b, 19 c) occurssubstantially instantaneously according to a stepped function.
 18. Themethod according to claim 16, wherein the step of changing the relativequantities for mixture of the components (18 a, 18 b, 18 c, 19 a, 19 b,19 c) occurs continuously according to a gradual function.
 19. Themethod according to any of the foregoing claims from 16 to 18, whereinthe chemico-physical properties comprise the level of porosity of themembrane (2).
 20. The method according to any of the foregoing claimsfrom 16 to 19, further comprising the step of inserting stiffeningelements (45) in the membrane (2) during membrane (2) formation.
 21. Themethod according to any of the foregoing claims from 16 to 19, furthercomprising the step of heating a zone (48) close to a support (11)forming an element (37) on which the fluid substances sprayed aredeposited and build up.